Integrated Transcriptomic and Network Pharmacology Identifies IRF1, PTGS2, TNF, and IFNG as Candidate Targets of Cortex Dictamni in Atopic Dermatitis

Cortex Dictamni has been used in traditional Chinese medicine (TCM) for inflammatory skin disorders, but its potential molecular targets in atopic dermatitis (AD) remain incompletely characterized. Active compounds and predicted targets of Cortex Dictamni were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and integrated with bulk-transcriptomic differential-expression data and single-cell RNA-sequencing data. Protein-protein interaction, functional-enrichment, gene set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA)-based immune-cell and pathway analyses were performed with Benjamini-Hochberg correction for multiple testing. Molecular docking was used to predict luteolin-IFNG and β-sitosterol-PTGS2 binding poses, and candidate-gene expression was assessed in TNF-α/IFN-γ-stimulated HaCaT keratinocytes treated with low concentrations of purified dictamnine. Eighteen active components yielded 170 predicted targets; 88 overlapped with AD-related genes, and 43 of these were differentially expressed. Intersecting 366 cell-type-specific differentially expressed genes with 42 targets identified IRF1, PTGS2, TNF, and IFNG. IRF1, PTGS2, and TNF were upregulated in specific immune-cell populations, whereas IFNG was downregulated in natural killer cells. Ribosome-pathway enrichment was observed across five immune-cell types. After Benjamini-Hochberg correction, immune-signature correlations were gene-specific and bidirectional, whereas Hallmark-pathway correlations were nonsignificant. Docking predicted possible binding poses for luteolin-IFNG and β-sitosterol-PTGS2. In TNF-α/IFN-γ-stimulated HaCaT cells, 6.25 and 12.5 µM dictamnine reduced all four mRNAs, whereas 12.5 µM dictamnine alone had no significant effect. Collectively, IRF1, PTGS2, TNF, and IFNG were nominated as potential Cortex Dictamni-associated targets in AD, and low-dose purified dictamnine provided preliminary mRNA-level support. These findings do not establish crude-herb efficacy or direct target-compound interactions and require protein-level, mechanistic, in vivo, and clinical validation.